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Shwachman-Diamond syndrome (SDS) is a rare autosomal recessive disorder with an incidence of 1 in 50.000 births. In 2001, the genetic defect of SDS was mapped to the centromeric region of chromosome 7 and in 2003 the defect was narrowed down to a single gene, which was named the Shwachman-Bodian-Diamond Syndrome (SBDS) gene. The mutations in the SBDS gene were identified in 90% of patients. Pancreatic exocrine insufficiency, bone marrow dysfunction with peripheral blood cytopenias, skeletal abnormalities, short stature and immune dysfunction characterize the disorder. Neutropenia plays a crucial role in the occurrence of recurrent and severe infectious complications representing one of the major causes of death in SDS patients. The aim of our study is to better comprehend the marrow dysfunction occurring in SDS patients, by analysing the functional properties of bone marrow (BM)-derived mesenchymal stem cells (MSCs). BM cells obtained from patients and healthy donors (HDs) were plated in sterile tissue culture flasks. At the third passage of the culture, cells were tested for the expression of specific surface markers, their ability to differentiate into mesengenic lineages, their capability to abrogate T cell proliferation and their ability to prevent neutrophil apoptosis. MSCs derived from SDS patients (SDS-MSCs) displayed typical fibroblastoid morphology; they were consistently devoid of contaminating hematopoietic cells, being negative for CD34, CD45, HLA-DR, CD11b, CD19, and CD14, but expressed common MSC markers including CD90, CD73, CD105 and HLA-ABC. Similarly to MSCs obtained from healthy donors (HD-MSCs), these cells were able to differentiate into adipocytes, osteoblasts and chondrocytes. In addition, SDS-MSCs drastically decreased the mitogen-induced lymphocyte proliferation, in a dose dependent manner. We also cultured neutrophils obtained from HD in presence or absence of MSCs at different time points. We demonstrated that SDS-MSCs were comparable to H

The management of congenital and acquired neutropenias presents some differences according to the type of the disease. Treatment with recombinant human granulocyte-colony stimulating factor (G-CSF) is not standardized and scanty data are available on the best schedule to apply. The frequency and the type of longitudinal controls in patients affected with neutropenias are not usually discussed in the literature. The Neutropenia Committee of the Marrow Failure Syndrome Group (MFSG) of the Associazione Italiana di Emato-Oncologia Pediatrica (AIEOP) elaborated this document following design and methodology formerly approved by the AIEOP board. The panel of experts reviewed the literature on the topic and participated in a conference producing a document that includes recommendations on neutropenia treatment and timing of follow-up. © 2011 Wiley Periodicals, Inc.

There are many types of cancers in children that are very different from those found in adults: leukaemia, lymphoma, and brain tumours are rather common in children. Acute lymphoblastic leukaemia (ALL) is the most common type of malignancy encountered. The role of pediatric dentist is very important before, during and after therapy: up to 24% of life-threatening infections arise from oral sites and areas. Early dental intervention and preventions procedures may significantly reduce oral complications associated with myelosuppressive cancer treatment. It is really important to evaluate the oral health surveys and to cut out potential sources of infection in mouth in these patients concurrent with their medical therapy. The aim of this review is summarizing the main features of oral mucositis in Childhood Acute Lymphoblastic Leukaemia, providing a little review for the approach, diagnosis and treatment of oral mucositis of ALL, which is frequent and potentially dangerous: it's important considering oral lesions of this type of childhood cancer in order to prevent complications before, during and after chemo or radio therapy to improve the quality of life of little patients

In the past two decades, childhood acute lymphoblastic leukemia (ALL) cure rate has reached over 80% due to treatment advances, but some resistant ALL subtypes, such as those that carry the Philadelphia (Ph+) chromosome, still don’t respond to therapy. The presence of BCR-ABL in ALL children is correlated to a very poor prognosis, nevertheless, several long-scale studies have shown that Ph+ ALL is heterogeneous in terms of clinical parameters and patients respond differently to the therapy, what suggests the presence of additional mechanisms of leukemogenesis. A set of international studies with large series of patients have shown that an earlier remission after induction with glucocorticoids and intrathecal methotrexate (IT MTX) is correlated to a better outcome. In the present study we looked for secondary genetic lesions in a group of 78 consecutive Ph+ ALL children diagnosed in Italy between 2000 and 2010, specifically studying deletions in the IKZF1 gene and the miRNA profile according to the first therapy response. The IKZF1 gene was studied by PCR, direct sequencing and SNP array and a high incidence of deletions (70%) was detected in our children, specially the d4-7(62%). The miRNA signature was analysed by miRNA array comparing two groups of patients differentiated according to MRD/prednisone response. Particularly miR-221, 222 and miR-125b-2 are highly overexpressed in the poor responder group of patients. We showed in vivo that miR-125b-2 acts as oncogene and increases leukemia aggressiveness. Further studies will be necessary to understand how IKZF1, miR-221,222 and 125b act in cooperation with BCR-ABL to induce leukemia. In the future, novel target therapies can emerge as pro-apoptotic approaches to be added to the anti-tyrosine kinase drugs in order to improve response and survivor in Ph+ ALL.

In the first part of our work we focused our attention on the biological question about the differences between two pathologies: T-cell lymphoblastic leukemia and T-cell lymphoblastic lymphoma. These two diseases share many features such as immunophenotypic features, lymphoblast morphology and clinical characteristics and are differentially diagnosed only on the base of bone marrow involvement. We tried to understand whether T-cell leukemia and lymphoma are a unique pathology with a different manifestation or whether they are two different diseases. The results obtained by gene expression profiling revealed an intrinsic difference in the expression of 78 genes between T-ALL and T-LBL. In particular since these genes belong to the angiogenesis and the chemotactic response we supposed that the two malignancies have different ability to respond to several cyto- and chemokines and that T-LBL need to modulate transcription to promote angiogenesis as well as to deal with hypoxic conditions. Also by analysis of copy number we were able to identify some abnormalities that seemed to be specific for each group regardless the limited data set of patients. Although this work provides additional elements in the characterization of these two pathologies, many studies have yet to be done, especially on the comprehension of the different capability of cells to migrate and invade the bone marrow compartment. The complete understanding of the molecular characteristics of T-LBL and T-ALL represents the driving element toward the design of fully successful therapeutic approaches. The second part of the study focused on the genetic characterization of two different groups of T-ALL patients on the basis of MRD response. With the aim to find biological correlates with the outcome for HR and nonHR patients, we performed many analyses, starting from copy number analysis to microRNAs expression profiling. Furthermore, we tried to integrate all the data in order to delineate common c

Children, particularly in their first years, are exposed to a variety of potentially dangerous situations, also in their natural environment, at home. The finding of a death child in his bed during unattended afternoon sleep, could be a critical situation in death’s investigation. Each hypothesis – natural or accidental death, neglect or filicide – has to be evaluated from the beginning. Filicide - the murder of one’s own child - is a vast crime, but not only the fairly home arrangements of a young couple of parents, can lead to exclude such a hypothesis. We present a case where a 17 month old boy was found hanging, with the head entrapped between the mattress and the wooden crib rails. To help the forensic evaluation of this suspect accidental asphyxial death, the reconstruction of the position of the body in the bed and a careful examination of the structure - wooden protection crib rails - of the bed itself.

Congenital and acquired neutropenia are rare disorders whose frequency in pediatric age may be underestimated due to remarkable differences in definition or misdiagnosed because of the lack of common practice guidelines. Neutropenia Committee of the Marrow Failure Syndrome Group (MFSG) of the AIEOP (Associazione Italiana Emato-Oncologia Pediatrica) elaborated this document following design and methodology formerly approved by the AIEOP board. The panel of experts reviewed the literature on the topic and participated in a conference producing a document which includes a classification of neutropenia and a comprehensive guideline on diagnosis of neutropenia. © 2011 Wiley-Liss, Inc.

the chpater presents the cognitive-constructive model applied to the field of eating disorders in children, emphasizing in particular the role of emotions and emotion regulation and disregulation in onset, maintenance and outcome of eating abnormal behaviour

The author presents the cognitive-constructivist clinical model and the role of emotions in interpersonal processes. individual differences and developmental stages of individual with an eating disorder are described in the chapter. a specific attention - supported by experimental evidences - is given to core emotions (e.g. loneliness, vulnerability to judgement). the chapter ends with some reflections on psychological intervention in education

the paper presents an overview of eating disorders in childhood and treatment

A total of 123 community paediatricians and 23 microbiology laboratories studied the clinical and bacteriological efficacy of treatment of group A streptococcal pharyngitis in Italy. Of 1065 patients, from whom Streptococcus pyogenes was isolated, 723 returned to follow up and of these 138 (19%) still had a positive throat culture. The erythromycin resistance (ER) rate was 23.7% with resistance phenotype distribution of: 31.7% constitutive (CR), 26.6% inducible (IR) and 41.7% efflux pump (M) resistance phenotype. All strains were susceptible to the beta-lactam agents tested. CR strains were highly resistant to all 14, 15 and 16 membered macrolides with the exception of rokitamycin which showed activity against 37.8% of isolates. All phenotype M and some IR isolates were susceptible to clindamycin, rokitamycin, josamycin and spiramycin; clarithromycin was active against a small percentage of strains belonging to the IR and M phenotype. Bacterial eradication was found in 85.5, 78.7 and 75.8% of the penicillin, macrolide and cephalosporin treated groups. Genotyping of strains showed that 8.7% of the 19% of cases classified as 'failed bacterial eradication' were due to recolonization with a different isolate, observed exclusively among beta-lactams treated patients. Clinical cure was achieved in a high percentage of cases, irrespective of the antibiotic prescribed, with the best clinical efficacy being found following therapy with amoxycillin and clarithromycin (90.9%).

A retrospective analysis of susceptibility data available for Group A streptococcal isolates collected between January 1990 and January 1996 at the Hospital Microbiology Laboratory of Monza (North Italy), showed a sharp rise in the erythromycin resistance rates during the last 3 years. Streptococcus pyogenes resistant to erythromycin accounted for approximately 1% of strains isolated between 1990 and 1992; the percentage then rose from 5% in 1993 to almost 39% in 1995. In January 1996, the resistance rates peaked to 81%. A prospective controlled study performed between March and May of 1996 to determine the percentage of erythromycin-resistant Group A streptococci isolated in Monza from untreated children with acute pharyngo-tonsillitis, gave further confirmation of a high rate of erythromycin resistance (47%) in this area. Molecular characterization by T-serotyping and pulse-field gel electrophoresis analysis of 25 erythromycin-resistant Group A streptococcal isolates, showed a relatively high degree of heterogeneity among these strains, demonstrating that the increased resistance is not caused by the spread of a single clone